Coronary artery disease has been the leading causes of death in the United States for several decades and this has led to a search for factors that contribute to the mortality and morbidity risks. Cholesterol has long been known as a risk factor, but recently emphasis has shifted to the carriers of cholesterol, the lipoproteins, and their constituent proteins, the apolipoproteins. We propose here to investigate the genetics and epidemiology of apolipoproteins levels (A-I, A-II, B, C-II, C-III, and E) in a sample of 2200 Mexican-Americans aged 15 to 75 years residing in Starr County, Texas, on whom extensive clinical, dietary and metabolic information is or will be available and from whom blood samples will be made available for these investigations (approximately 390 individuals examined prior to the start of this project will be recontacted to obtain a fresh blood sample). This opportunistic sample will consist of 1000 randomly selected individuals from whom 100 probands will have been identified as having gallbladder disease. The remaining 1200 individuals will consist of first degree relatives of these probands. Additionally 100 control individuals and their spouses will have been identified and followed longitudinally for five years. It is only because of recent developments of commercial assays for these determinations that makes this project feasible on the scale (and budget) proposed. Baseline distributions for each of these factors and the effects of age, sex, body mass and fat distribution, diet, smoking and drinking will be determined. Additionally, we will elucidate the relationships that exist between these factors and their contributions to the risk individuals have of developing disease. From the longitudinal data we will assess the dynamics of changes in apolipoprotein levels and profiles and those factors which contribute to their change. The random and longitudinal data will be coupled with the pedigree data to determine the effects of major genes, polygenes, and environments on the variability of each apolipoprotein and on the relationships between these and other risk factors.